Restricted accessResearch articleFirst published online 2025-01
Baicalin Attenuates Diabetic Cardiomyopathy In Vivo and In Vitro by Inhibiting Autophagy and Cell Death Through SENP1/SIRT3 Signaling Pathway Activation
Diabetic heart damage can lead to cardiomyocyte death, which endangers human health. Baicalin (BAI) is a bioactive compound that plays an important role in cardiovascular diseases. Sentrin/SUMO-specific protease 1 (SENP1) regulates the de-small ubiquitin-like modifier (deSUMOylation) process of Sirtuin 3 (SIRT3) and plays a crucial role in regulating mitochondrial mass and preventing cell injury. Our hypothesis is that BAI regulates the deSUMOylation level of SIRT3 through SENP1 to enhance mitochondrial quality control and prevent cell death, ultimately improving diabetic cardiomyopathy (DCM).
Results:
The protein expression of SENP1 decreased in cardiomyocytes induced by high glucose and in db/db mice. The cardioprotective effects of BAI were eliminated by silencing endogenous SENP1, whereas overexpression of SENP1 showed similar cardioprotective effects to those of BAI. Furthermore, co-immunoprecipitation experiments showed that BAI’s cardioprotective effect was due to the inhibition of the SUMOylation modification level of SIRT3 by SENP1. Inhibition of SENP1 expression resulted in an increase in SUMOylation of SIRT3. This led to increased acetylation of mitochondrial protein, accumulation of reactive oxygen species, impaired autophagy, impaired mitochondrial oxidative phosphorylation, and increased cell death. None of these changes could be reversed by BAI.
Conclusion:
BAI improves DCM by promoting SIRT3 deSUMOylation through SENP1, restoring mitochondrial stability, and preventing the cell death of cardiomyocytes.
Innovation:
This study proposes for the first time that SIRT3 SUMOylation modification is involved in the development of DCM and provides in vivo and in vitro data support that BAI inhibits cardiomyocyte ferroptosis and apoptosis in DCM through SENP1. Antioxid. Redox Signal. 42, 53–76.
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